Camel Whey Protein Protects B and T Cells from Apoptosis by Suppressing Activating Transcription Factor-3 (ATF-3)-Mediated Oxidative Stress and Enhancing Phosphorylation of AKT and IκB-α in Type I Diabetic Mice

被引:24
作者
Badr, Gamal [1 ,2 ]
Sayed, Leila H. [1 ,2 ,3 ]
Omar, Hossam El-Din M. [1 ,3 ]
Abd El-Rahim, Ali M. [4 ]
Ahmed, Emad A. [1 ,2 ]
Mahmoud, Mohamed H. [5 ,6 ]
机构
[1] Assiut Univ, Fac Sci, Zool Dept, Assiut 71516, Egypt
[2] Assiut Univ, Fac Sci, Zool Dept, Lab Immunol & Mol Physiol, Assiut, Egypt
[3] Assiut Univ, Fac Sci, Zool Dept, Lab Physiol, Assiut, Egypt
[4] Assiut Univ, Fac Agr, Dairy Dept, Assiut, Egypt
[5] King Saud Univ, Deanship Sci Res, Riyadh, Saudi Arabia
[6] Natl Res Ctr, Food Sci & Nutr Dept, Cairo, Egypt
关键词
Apoptosis; Camel whey protein; Diabetes mellitus; Free radicals; Lymphocytes; MILK-PROTEINS; SILICA NANOPARTICLES; BREAST-CANCER; GROWTH-FACTOR; MOUSE MODEL; BEE VENOM; LACTOFERRIN; PROLIFERATION; KINASE; VIRUS;
D O I
10.1159/000455935
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background: Diabetes mellitus (DM) is associated with severe immune system complications. Camel whey protein (CWP) decreases free radicals (ROS) and modulates immune functions, but its effect on DM-impaired immune systems has not been studied. We investigated the impact of CWP on the immune system in a Type 1 diabetes mouse model. Methods: Three experimental groups were used: (1) non-diabetic control; (2) diabetic; and (3) CWP-treated diabetic mice. Results: Induction of diabetes by streptozotocin was associated with reduction of body weight and insulin level, increase in glucose level and pro-inflammatory cytokines (IL-1 beta, IL-6, and TNF-alpha), and reduction in IL-2 and IL-4 levels. Upregulated ATF-3 expression was followed by a marked elevation in ROS levels. Lymphocytes from diabetic mice exhibited increased apoptosis through decreased phosphorylation of AKT and I kappa B-alpha, increased infiltration of T cells in the spleen and thymus, and decreased B cell numbers in the spleen. Supplementation with CWP decreased the levels of proinflammatory cytokines, ROS, and ATF-3 expression, and increased the levels of IL-4. Treatment with CWP decreased apoptosis by enhancing the phosphorylation of AKT and I kappa B-alpha. as well as T-cell and B-cell distribution in the spleen and thymus. Conclusions: Our findings suggest the beneficial effects of CWP supplementation during diabetes on decreasing and orchestrating the redox status and subsequently rescuing the immune cells from exhaustion. (C) 2017 The Author(s) Published by S. Karger AG, Basel
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页码:41 / 54
页数:14
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共 64 条
[51]  
Nakagomi S, 2003, J NEUROSCI, V23, P5187
[52]   Expression of transcriptional repressor ATF3/LRF1 in human atherosclerosis: colocalization and possible involvement in cell death of vascular endothelial cells [J].
Nawa, T ;
Nawa, MT ;
Adachi, MT ;
Uchimura, I ;
Shimokawa, R ;
Fujisawa, K ;
Tanaka, A ;
Numano, F ;
Kitajima, S .
ATHEROSCLEROSIS, 2002, 161 (02) :281-291
[53]   ATF3 inhibits doxorubicin-induced apoptosis in cardiac myocytes: A novel cardioprotective role of ATF3 [J].
Nobori, K ;
Ito, H ;
Tamamori-Adachi, M ;
Adachi, S ;
Ono, Y ;
Kawauchi, J ;
Kitajima, S ;
Marumo, F ;
Isobe, M .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2002, 34 (10) :1387-1397
[54]   DIETARY MILK-PROTEINS INHIBIT THE DEVELOPMENT OF DIMETHYLHYDRAZINE-INDUCED MALIGNANCY [J].
PAPENBURG, R ;
BOUNOUS, G ;
FLEISZER, D ;
GOLD, P .
TUMOR BIOLOGY, 1990, 11 (03) :129-136
[55]   Antiarthritic effect of bee venom -: Inhibition of inflammation mediator generation by suppression of NF-κB through interaction with the p50 subunit [J].
Park, HJ ;
Lee, SH ;
Son, DJ ;
Oh, KW ;
Kim, KH ;
Song, HS ;
Kim, GJ ;
Oh, GT ;
Yoon, DY ;
Hong, JT .
ARTHRITIS AND RHEUMATISM, 2004, 50 (11) :3504-3515
[56]   Role of NF-κB in the pathogenesis of diabetes and its associated complications [J].
Patel, Sandip ;
Santani, Dev .
PHARMACOLOGICAL REPORTS, 2009, 61 (04) :595-603
[57]   Screening the anti infectivity potentials of native N- and C-lobes derived from the camel lactoferrin against hepatitis C virus [J].
Redwan, Elrashdy M. ;
EL-Fakharany, Esmail M. ;
Uversky, Vladimir N. ;
Linjawi, Mustafa H. .
BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE, 2014, 14
[58]   A Bovine Whey Protein Extract Stimulates Human Neutrophils to Generate Bioactive IL-1Ra through a NF-κB- and MAPK-Dependent Mechanism [J].
Rusu, Daniel ;
Drouin, Rejean ;
Pouliot, Yves ;
Gauthier, Sylvic ;
Poubelle, Patrice E. .
JOURNAL OF NUTRITION, 2010, 140 (02) :382-391
[59]  
Saltanat Heinayat, 2009, Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, V25, P431
[60]   Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex [J].
Sarbassov, DD ;
Guertin, DA ;
Ali, SM ;
Sabatini, DM .
SCIENCE, 2005, 307 (5712) :1098-1101